Circulating endothelial cells, microparticles and progenitors: key players towards the definition of vascular competence

Abstract

The balance between lesion and regeneration of the endothelium is critical for the maintenance of vessel integrity. Exposure to cardiovascular risk factors (CRF) alters the regulatory functions of the endothelium that progresses from a quiescent state to activation, apoptosis and death. In the last 10 years, identification of circulating endothelial cells (CEC) and endothelial-derived microparticles (EMP) in the circulation has raised considerable interest as non-invasive markers of vascular dysfunction. Indeed, these endothelial-derived biomarkers were associated with most of the CRFs, were indicative of a poor clinical outcome in atherothrombotic disorders and correlated with established parameters of endothelial dysfunction. CEC and EMP also behave as potential pathogenic vectors able to accelerate endothelial dysfunction and promote disease progression. The endothelial response to injury has been enlarged by the discovery of a powerful physiological repair process based on the recruitment of circulating endothelial progenitor cells (EPC) from the bone marrow. Recent studies indicate that reduction of EPC number and function by CRF plays a critical role in the progression of cardiovascular diseases. This EPC-mediated repair to injury response can be integrated into a clinical endothelial phenotype defining the 'vascular competence' of each individual. In the future, provided that standardization of available methodologies could be achieved, multimarker strategies combining CEC, EMP and EPC levels as integrative markers of 'vascular competence' may offer new perspectives to assess vascular risk and to monitor treatment efficacy.

1

Mechanical damage or chronic exposure to CRF alters the regulatory functions of the endothelium which progress to apoptosis and dysfunction. Disruption of endothelial integrity is associated with a broad spectrum of responses including detachment of mature endothelial cells (CEC) and shedding of endothelial microparticles (EMP). In response to injury, endothelial progenitors cells (EPC), recruited from the bone marrow, are able to differentiate into mature cells and to restore endothelial integrity. These endothelial responses can be integrated into a dynamic ‘activation / lesion/regeneration triad’ CRF: cardiovascular risk factor, CEC: circulating endothelial cells, EMP: endothelial microparticles, EPC: endothelial progenitor cells.

2

Endothelial integrity is viewed as a balance between endothelial injury reflected by CEC and EMP, and endogenous capacity for repair attested by EPC. The net result of this equilibrium can be integrated into a clinical endothelial phenotype defining vascular competence. Multimarker strategies combining CEC, EMP and EPC to define Vascular Competence Index are promising to evaluate at the individual level the impact of cardiovascular risk factors on disease progression. Such mul-timarker approach may also provide relevant tools for delineation and monitoring of therapeutic strategies or life style modifications aimed to improve endothelial function by limiting damage and/or reinforce regenerative mechanisms. CEC: circulating endothelial cells, EMP: endothelial microparticles, EPC: endothelial progenitor cells, VCI: vascular competence index.